Summary

• The company cannot recommend any practices, procedures, or usage that deviates from the approved labeling.
• Velasco et al (2024)¹ reported results from a per-protocol analysis of an investigator-initiated, non-randomized, single-arm study that analyzed TREMFYA 100 mg in adult patients (N=12) with moderate to severe pityriasis rubra pilaris (PRP).
  • Out of 12 patients, 9, 5, and 4 patients achieved Psoriasis Area and Severity Index (PASI) 50, PASI 75, and PASI 90, respectively at week 24.
• Cutler et al (2021)² reported results from an interim analysis of an ongoing investigatorinitiated, single-arm study that analyzed the use of TREMFYA 100 mg in patients (N=6) with moderate to severe PRP; body surface area [BSA] ≥10%.
  • Of the 6 patients who completed 24 weeks of treatment, 5 experienced >50% improvement in the PASI score.
• There are additional data on the use of TREMFYA in patients with PRP from case reports.^3-6

CLINICAL DATA

Velasco et al (2024)¹ reported results from a per-protocol analysis of an investigator-initiated, non-randomized, single-arm study that analyzed TREMFYA 100 mg in adult patients (N=12) with moderate to severe PRP with an affected BSA ≥10%.

• Patients received TREMFYA 100 mg subcutaneous (SC) injection at weeks 0, 4, 12, and 20. The primary endpoint was the mean change in the PASI score from baseline to week 24. The secondary endpoints included pruritus, Dermatology Life Quality Index (DLQI) score, and clinical response at week 36.
• In this per-protocol analysis, 2 patients (1 patient lost to follow-up after week 20 visit and 1 patient died after week 12 visit) did not complete the study and 12 patients (male, 8; female, 4; mean age, 56.5 years) were included for assessment.^1,7
• The mean (standard deviation [SD]) PASI score decreased from week 0 (30.6 [11.4]) to week 24 (18.9 [12.5]; P<0.001; 95% confidence interval [CI], 11.0-26.8).
  • The mean improvement in the PASI score was 61.8% at week 24.
  • PASI 50, 75, and 90 was defined as reduction in PASI score by at least 50%, 75%, and 90% respectively.
  • Out of 12 patients, 9, 5, and 4 patients achieved PASI 50, PASI 75, and PASI 90, respectively at week 24.
  • All 9 patients who achieved PASI 50 at week 24 had further improvement at week 36 with a reduction in the mean (SD) PASI score from week 24 (7.9 [2.8]) to week 36 (2.8 [3.5]; P=0.01; 95% CI, 1.7-6.9).
  • At the week 36 follow-up, 8 and 6 patients achieved PASI 75 and PASI 90, respectively.
• The mean (SD) DLQI score decreased from week 0 (20.1 [6.8]) to week 24 (12.2 [7.8]; P<0.001; 95% CI, 7.3-17.2).
  • The mean improvement in the DLQI score was 60.2% at week 24.
  • Overall, 11 out of 12 patients achieved a ≥4-point improvement in the DLQI score at week 24, with 2/12 and 7/12 patients reaching a DLQI score of 0 and ≤5, respectively.
• The mean (SD) improvement in itch numeric rating scale (0-10 point) score decreased from week 0 (6.9 [2.2]) to week 24 (4.3 [3.5]; P<0.001; 95% CI, 1.1-5.1).
  • The mean improvement in itch numeric rating scale was 62.3% at week 24.
• Nine patients reported mild or moderate adverse events (AEs) and none led to interruptions in treatment protocol.
  • Mild AEs included temporary PRP worsening, ectropion worsening, elevated creatinine levels, gastroenteritis, weight loss, ground level fall, injection site reactions, scalp pustules, pulmonary nodule findings, and false-positive hyperkalemia.
  • Moderate AEs included COVID-19 infection, new diagnosis of type 2 diabetes, Bell’s palsy, otitis externa, leukocytosis presumed secondary to otitis media, herpes zoster infection, allergic contact dermatitis, fall due to painful plantar fissures, motor vehicle collision, and ruptured bulla on the hand.
• One serious AE not associated with the treatment was reported.
  • The patient was hospitalized for cholecystitis and later experienced a myocardial infarction that led to death before the end of the treatment period.

Cutler et al (2021)² reported results from an interim analysis of an ongoing, investigatorinitiated, single-arm study that analyzed the use of TREMFYA 100 mg in patients with moderate to severe PRP (BSA ≥10%). Patients received TREMFYA 100 mg SC injection at weeks 0, 4, 12, and 20. Study endpoints included both investigator- and patient-reported outcomes. The primary endpoint was the change in the PASI score from baseline to week 24.

• For this interim analysis, 6 patients (male, 4; female, 2; median age, 59.5 years) were included for assessment through 24 weeks.
• An intention-to-treat analysis was conducted.
• Mean (SD) clinician-assessed severity (measured by PASI) decreased from week 0 (31.4 [13.5]) to week 24 (10.8 [10.5]; P=0.0159).
• Of the 6 patients, 5 experienced >50% improvement in the PASI score and 1 did not complete the study due to lack of improvement.
• Mean (SD) patient-reported quality of life (measured by DLQI) improved from week 0 (21.3 [5.7]) to week 24 (9.5 [9.4]; P=0.0074).

Case Reports

Pham et al (2022)³ reported a case series of 2 patients with refractory type 1 PRP.

• Two male patients (patient 1 aged 69, patient 2 aged 63) presented with progressive papulosquamous erythroderma and palmoplantar keratoderma.
• Patient 2 presented with progressive scaling erythroderma with island of sparing and palmoplantar keratoderma, developing over 4-6 months and associated with significant pruritus. The patient also had a secondary congestive cardiac failure due to erythroderma. Mild acanthosis with thick suprapapillary plate, mildly lengthened rete ridges, checkerboard parakeratosis, patchy basal vacuolization and mild superficial dermal lymphocytic/histiocytic inflammation with occasional eosinophils and neutrophils were observed. Prior therapies included topical corticosteroid wet dressing, oral prednisolone, acitretin, and cyclosporine.
• Ustekinumab 90 mg SC at week 0, 4, 12, and then every 12 weeks thereafter was initiated for patient 2 at 14 months after initial onset of PRP. Significant improvement of erythroderma was reported at week 4 and complete clearance of body involvement was reported at 6 months. Supplemental topical therapy and topical Psoralen-ultraviolet A (PUVA) phototherapy were also utilized for palmoplantar keratoderma.
• TREMFYA 100 mg SC at week 0, 4, 8, and every 8 weeks (Q8W) thereafter was later initiated, replacing ustekinumab therapy, due to recrudescence of palmoplantar keratoderma at 12 months, along with reduced effect at the 8-week mark for erythrodermic involvement. Complete resolution of palmoplantar keratoderma was reported and sustained at 12 months.
• No significant treatment-related AEs were reported during either ustekinumab or TREMFYA therapy.

Nishimura et al (2022)⁴ reported the use TREMFYA, in combination with cyclosporine for the treatment of type 1 PRP.

• A male patient in his 60s presented with erythematous indurative plaque with pityriasis-like desquamation on his forehead and keratotic papules consistent with pores on his trunk. The patient was previously diagnosed with atopic dermatitis with no symptom alleviation for 2 years.
• Clinical and pathological findings indicated the presence of PRP: Diagnosis was confirmed with biopsy which revealed acanthosis and psoriasiform hyperplasia in the epidermis and horn cysts in the follicles. A keratin plug was observed in the follicular structures. Parakeratotic foci were identified in the horny layer of the orthokeratosis. Inflammatory cell infiltration from the basal layer of the epidermis to the dermis mainly comprised of lymphocytes.
• Oral methotrexate, etretinate, and brodalumab were trialed unsuccessfully.
• Cyclosporine was initiated at 100 mg/day and skin rash was improved within 1 week. After dosage was reduced to 50 mg/day due to decreased renal function, patient showed signs of relapse.
• TREMFYA 100 mg SC at weeks 0 and 4, and then Q8W was initiated (no abnormalities were found in pre-treatment screening).
• Improvement in PRP symptoms was reported at week 12 without any adverse effects.
• Complete remission remained at 9 months. After 1 year of TREMFYA therapy, cyclosporine was discontinued, and symptoms remained well-controlled.

Pilz et al (2019)⁵ reported the use of TREMFYA for the treatment of 2 patients with suberythrodermic PRP.

Presentation and Diagnostic Assessment

• Two male patients (patient 1 aged 65 years and patient 2 aged 75 years) presented with a history of generalized erythema and pruritus for 8-12 weeks, static Physician's Global Assessment (sPGA) score of 5/5 (both patients), DLQI score of 15/30 and 19/30, respectively, involved BSA of 95% and 98%, respectively, peak pruritus of 9/10 and 3/10 on a numeric rating scale, respectively, and salmon-colored erythroderma interspersed with well-distinguished areas of unaffected skin (nappes claires).
• A diagnosis of suberythrodermic PRP was made on the basis of acanthosis with broad rete ridges, confluent hypergranulosis, and alternating orthokeratosis and parakeratosis in the histological analysis and superficial perivascular lymphocytic infiltrate in the dermal biopsy.
• Both patients had received topical and oral corticosteroids for 10 weeks. Patient 1 had also received acitretin.
• A distinct IL-17 expression was observed in the immunohistochemical analysis of lesional skin biopsy from both patients.

Treatment and Follow-up

• Both patients were initiated with TREMFYA 100 mg SC at weeks 0 and 4, and then Q8W.
• The response at week 16 included a decrease in the DLQI score to 1 in patient 1 and 2 in patient 2, a reduction in the sPGA score to 1 in both patients, and a decrease in affected BSA to 5% in patient 1 and 15% in patient 2.
• No AEs were reported.

Nagai et al (2020)⁶ describe a case report of a 47-year-old female patient diagnosed with type 1 PRP.

Presentation and Diagnostic Assessment

• Patient presented with a 3-month history of pruritic erythema, which began on the scalp then spread to the face, trunk, arms, palms, and thighs.
• Psoriasiform epidermal hyperplasia, hyperkeratosis with alternating orthokeratosis and parakeratosis, and superficial perivascular dermal lymphocytic infiltrate were revealed upon conduction of histological analysis.
• No abnormalities except for a mild elevation in serum lactate dehydrogenase and aspartate aminotransferase levels were found in blood tests.
• Patient was negative for anti-human immunodeficiency virus antibody.

Treatment and Follow-up

• Patient was treated with oral etretinate 30 mg/day, which was ineffective and stopped due to side effects (liver injury).
• Oral apremilast and bath- PUVA phototherapy were combined with a class 1-2 topical steroid but showed no beneficial therapeutic effect.  
• During these treatments, patient’s erythema spread and the percentage of affected BSA and sPGA reached 90% and 5 respectively.
• Patient was initiated on SC TREMFYA 100 mg.
• After 4 weeks, patient’s erythema decreased, and the SC TREMFYA 100 mg was repeated.
• TREMFYA administration continued at Q8W intervals thereafter.
• At 24 weeks after the initial injection, BSA and sPGA reduced to 2% and 1, respectively, and TREMFYA was discontinued.
• At 38 weeks after the initial injection, erythema and pruritus were absent and no relapse occurred at 36 weeks after the last injection.

LITERATURE SEARCH

A literature search of MEDLINE^®, Embase^®, BIOSIS Previews^®, and Derwent Drug File databases (and/or other resources, including internal/external databases) was conducted on 22 July 2024.